title: Reduction of bitterness of antihistaminic drugs by complexation with β-cyclodextrins.
abstract: Reduction of bitterness of antihistaminic drugs by cyclodextrin (CyD) complexation was examined. The stability constant (Kc) of the 1:1 CyD inclusion complexes with antihistaminic drugs increased in the order of 2-hydroxypropyl-β-CyD (HP-β-CyD) ≈ β-CyD > γ-CyD > α-CyD for diphenhydramine and epinastine, and HP-β-CyD ≈ β-CyD > α-CyD > γ-CyD for hydroxyzine, cetirizine, and dl-chlorpheniramine. The inclusion complexes inhibited the adsorption of antihistaminic drugs to lipid membrane using liposomes, as the magnitude of Kc increased. From human gustatory sensation tests, β-CyD and HP-β-CyD potently suppressed the bitterness of antihistaminic drugs in a dose-dependent manner. Further, an artificial taste sensor analysis revealed that β-CyD and HP-β-CyD inhibited the bitterness of antihistaminic drugs in solution. The results suggest that CyDs suppress the bitterness of antihistaminic drugs in solutions through the formation of inclusion complexes. These results may provide useful information for masking or elimination of bitterness of drugs using CyDs.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Ono
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Takako
authors.initials: T
authors.lastname: Ishiguro
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Hirayama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iohara
authors.forename: Hakaru
authors.initials: H
authors.lastname: Seo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuruta
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
authors.forename: Kaneto
authors.initials: K
authors.lastname: Uekama
mesh_terms: D006633:Histamine Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D013649:Taste / Q000187:drug effects*; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D006633:Histamine Antagonists; D047392:beta-Cyclodextrins